L10, BCR and TCR expression

Question 1

what are the first steps to the generation of a functional BCR in developing B cells

Answer 1

recombination of heavy chain, D and J segments

Question 2

what happens after the first round of recombination (D and J segments)?

Answer 2

recombination of V and DJ segments. if this is successful, there is no recombination in allele #2 and kappa rearrangement is thereby induced

Question 3

what happens if second recombination of heavy chain is nonproductive with allele #1?

Answer 3

another recombination (V and DJ), but with allele #2 occurs. If productive, the micro heavy chain and the surrogate light chain form the pre-BCR and induces kappa rearrangement

Question 4

what happens if recombination with allele #2 is nonproductive?

Answer 4

the cell undergoes apoptosis

Question 5

what is the next step in BCR generation once a productive allele is used?

Answer 5

micro and kappa chains combine and inhibit rearrangement of kappa allele #2 and lambda rearrangement. the nonproductive allele does not combine with kappa chain - this forms the pre-BCR which can now allow recombination of light chain, lambda rearrangement occurs and so on until its unproductive…or death

Question 6

what is allelic exclusion in B cells?

Answer 6

the mechanism by which a single heavy chain and a single light chain from only one of the alleles are transcribed and translated into proteins

Question 7

what does the allelic exclusion in B cells contribute towards?

Answer 7

reduces the probabilities of generating auto-reactive BCR/antibodies … but is energetically expensive

Question 8

if avidity of the BCR is moderate, …

Answer 8

development of B cells continues

Question 9

what happens if avidity is high?

Answer 9

another round of light chain recombination can occur, known as receptor editing - this is a way of quality control that occurs in bone marrow

Question 10

what happens if avidity remains high, despite light chain recombination?

Answer 10

cell death or anergy (lack of energy)

Question 11

after BCR, stimulation of the B cells causes …

Answer 11

secretion of IgM (or IgD) anitbodies

Question 12

what is class switching?

Answer 12

Ig class swithces due to additional DNA recombination = Class Switch Recombination (CSR)

Question 13

what is affinity maturation?

Answer 13

when the binding strength of antibodies/BCR to antigens are “fine-tuned”/ small changes are made in the variable region - occurs by point mutations in the V genes = somatic hypermutation (SHM)

Question 14

how does signal transduction work through BCRs?

Answer 14

upon binding with an antigen, BCR associates with Ig Superfamily members Ig-alpha and Ig-beta (also known as CD79a and CD79b). this generates intracellular signals though immunoreceptor Tyrosine-based Activation Motifs (ITAM) - leads to activation and changes in the B cell

Question 15

what forms T-cell receptors (TCR)?

Answer 15

alpha and beta chains OR delta epsilon and sigma chains - the TCR is a membrane-bound heterodimer

Question 16

how must antigen binding and recognition by TCR occur?

Answer 16

must occur through antigen presentation by the correct MHC (major histocompatibility complex) molecule = MHC restriction

Question 17

where does allelic exclusion also occur?

Answer 17

T cells - TCR-beta chain, successful rearrangement of one beta allele prevents rearrangement of the second allele

Question 18

what are the different types of MHC restriction?

Answer 18

two types of no recognition and “self restriction” (3 types total). self restriction is the result of a need for the TCR to properly engage both MHC and a specific antigenic peptide.

no recognition (1 & 2): inability to engage the MHC results in a failure to recognize the bound Ag, or it is the correct Ag with the wrong MHC class molecule

Question 19

signal transduction through the TCR: like the BCR, the TCR has a short cytoplasmic tail that is ….

Answer 19

incapable of mediating intracellular signaling

Question 20

what is TCR signaling facilitated by?

Answer 20

accessory molecules: CD3 - transmembrane proteins with ITAM motifs on their cytoplasmic tails

Question 21

what is the role of co-receptors with TCR?

Answer 21

bind the invariant regions of the MHC molecules
1. CD4-MHCII (beta2 domain)
2. CD8-MHCI (alpha3 domain)

also act as markers to distinguish T Helper cells from Cytotoxic T cells (CD8+)

interacts with cytoplasmic tyrosine kinase Lck (signaling mediator)

increases sensitivity to the antigen a 100-fold